# HERV proteogenomics of narcotic-driven HIV latency

> **NIH NIH R61** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $722,475

## Abstract

Abstract
HIV eradication requires the elimination of latent reservoirs composed by cells harboring persistent proviruses.
The brain is an anatomical site that is poorly accessible to the immune system as well as therapeutic agents. It
also harbors a specific type of cells, microglia, where HIV can silently persist for long periods of time.
Human endogenous retroviruses (HERVs) are a group of transposable elements, which are mostly held in an
inactive state by different epigenetic mechanisms. Narcotic use induces changes the epigenetic landscape that
can influence latency establishment and HERV expression. This project’s goal is to test the hypothesis that the
distinct HERV expression signatures detected in HIV LTR-silent infection affect latency establishment and that
this can be influenced by narcotic treatment. Furthermore, latent HIV-specific HERV expression can be
exploited for the discovery of HIV latency specific markers. In order to investigate these hypotheses, it is
crucial to determine the precise identity of the HERV elements expressed during latency.
The experimental strategy is based on our newly developed reporter virus, which distinguishes latently infected
from productively infected microglia cells in combination with our established proteogenomic approach which
integrates HERV-specific RNA expression analysis with mass spec analysis. Such highly specialized
processing is required because of the repetitive nature of HERVs that so far has undermined their detailed
investigation. The RNA and protein expression blueprint obtained will inform on the ranking of the latent HIV-
specific HERVs whose relevance will be investigated utilizing state of the art CRISPR-based expression
induction in primary microglia as well as for the detection their expression in brain tissue form HIV patients with
and without documented history on narcotic use. We expect that the innovative experimental approach
proposed will provide insight into HERV RNA/protein expression landscapes in latently infected primary
microglia and offer potential causal links between latency establishment, HERV expression and substance
abuse.
Even though there are high-risk aspects in this proposal, the experimental strategy proposed will deliver
predictable, high gain benefits in our understanding of the complex biology underlying HIV latency in the brain
compartment.

## Key facts

- **NIH application ID:** 10930847
- **Project number:** 5R61DA058294-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** LUBBERTUS C MULDER
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $722,475
- **Award type:** 5
- **Project period:** 2023-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930847

## Citation

> US National Institutes of Health, RePORTER application 10930847, HERV proteogenomics of narcotic-driven HIV latency (5R61DA058294-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10930847. Licensed CC0.

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